Raftlin is involved in the nucleocapture complex to induce poly(I:C)-mediated TLR3 activation

Ayako Watanabe, Megumi Tatematsu, Kazuko Saeki, Sachiko Shibata, Hiroaki Shime, Akihiko Yoshimura, Chikashi Obuse, Tsukasa Seya, Misako Matsumoto

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46 Citations (Scopus)

Abstract

The double-stranded RNA analog, poly(I:C), extracellularly activates both the endosomal Toll-like receptor (TLR) 3 and the cytoplasmic RNA helicase, melanoma differentiation-associated gene 5, leading to the production of type I interferons (IFNs) and inflammatory cytokines. The mechanism by which extracellular poly(I:C) is delivered to TLR3-positive organelles and the cytoplasm remains to be elucidated. Here, we show that the cytoplasmic lipid raft protein, Raftlin, is essential for poly(I:C) cellular uptake in human myeloid dendritic cells and epithelial cells. When Raftlin was silenced, poly(I:C) failed to enter cells and induction of IFN-β production was inhibited. In addition, cellular uptake of B-type oligodeoxynucleotide that shares its uptake receptor with poly(I:C) was suppressed in Raftlin knockdown cells. Upon poly(I:C) stimulation, Raftlin was translocated from the cytoplasm to the plasma membrane where it colocalized with poly(I:C), and thereafter moved to TLR3-positive endosomes. Thus, Raftlin cooperates with the uptake receptor to mediate cell entry of poly(I:C), which is critical for activation of TLR3.

Original languageEnglish
Pages (from-to)10702-10711
Number of pages10
JournalJournal of Biological Chemistry
Volume286
Issue number12
DOIs
Publication statusPublished - 2011 Mar 25

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Watanabe, A., Tatematsu, M., Saeki, K., Shibata, S., Shime, H., Yoshimura, A., Obuse, C., Seya, T., & Matsumoto, M. (2011). Raftlin is involved in the nucleocapture complex to induce poly(I:C)-mediated TLR3 activation. Journal of Biological Chemistry, 286(12), 10702-10711. https://doi.org/10.1074/jbc.M110.185793